Sometimes you think you know a person and they suddenly surprise you by doing something so different that it is shocking or by taking on a new personality.

Cells can be that way too.

In my book on stem cells, Stem Cells: An Insider’s Guide (you can buy it here on Amazon–it’s very affordable–or also here at the publisher’s site for some international buyers) published last year, great scientific illustrator, Taylor Seamount, and I came up with a new adaptation (see image above) of a classic model of Waddington that visually explains how cells might change their personalities.

How would the STAP stem cell process fit into this model?

Cell biologist are increasingly viewing cells including stem cells as far more changeable than in the past. For example, one notion is that stem cells don’t really exist as a stable, concrete type of cell. This theory holds that the reality is rather much more complex and that cells can cycle between different identities and functions. For example, an ordinary cell might become a stem cell when under stress.

Yes, the STAP stem cell concept might fall into this larger model. Of course stem cells can also change into non-stem cells when they differentiate or perhaps when they are transformed into cancer cells.

In our Waddington adaptation, the cells are more potent the higher up on the hill they are. They can roll down the hill into different channels to end up with different fates such as death by falling into a chasm or differentiation into specific cell types like fat or skin cells. An alternate pathway, not previously included in Waddington models, allows for cells to transform into cancer cells. We’ve also got cells being dragged back up the hill to become iPS cells.

How would STAP fit into this kind of model? Maybe acid rain falling onto the landscape?

These kinds of models are both fun and helpful in promoting creative ways of thinking about cells and stem cells.

Dr. Knoepfler, I appreciate this question, very much. I am not too familiar with all the approaches, besides some small molecules like 5-azacytidine, for altering the epigenome. Are there a lot of physiological relevant ways to alter the epigenome?

If not, then it seems that whether or not STAP cells holds up, there is real potential in establishing an experimental approach for epigenome remodeling under physiologically relevant perturbation. One has to start thinking about inflammatory signaling as well. Plus the STAP cells, for right or wrong, reminds us that reprogramming has to converge on epigenetics, it just may be surprising that such a small number of transcription factors can be such potent drivers of epigenetics.

While for STAP cells, I am in the too good to be true camp, this part of the discovery seems exciting and promising.